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Cdx4 and menin co-regulate Hoxa9 expression in hematopoietic cells
Jizhou Yan1, Ya-Xiong Chen, Angela Desmond
1Abramson Family Cancer Research Institute, Department of Cancer Biology, Abramson Cancer Center, University of Pennsylvania, Philadelphia, Pennsylvania, United States of America.
Plos One
|December 22, 2006
Summary
Transcription factor Cdx4 and coregulator menin regulate Hoxa9 expression in hematopoietic cells. Menin controls Cdx4 binding and histone modifications at the Hoxa9 locus, impacting hematopoiesis.
Area of Science:
- Hematopoiesis research
- Molecular biology
- Epigenetics
Background:
- Transcription factor Cdx4 and menin are crucial for Hoxa9 gene expression.
- Normal hematopoiesis relies on Hoxa9 regulation.
- The exact mechanism of Hoxa9 regulation remains unclear.
Purpose of the Study:
- To elucidate the mechanism of Hoxa9 regulation by Cdx4 and menin.
- To investigate the role of histone modifications in Hoxa9 regulation.
Main Methods:
- Correlating Hoxa9 expression with histone modifications (H3K4M3).
- Assessing Cdx4 and menin binding to the Hoxa9 locus in vivo.
- Analyzing reporter gene activation and effects of menin ablation on Cdx4 binding and histone marks.
Main Results:
- Hoxa9 expression levels correlate with trimethylated histone H3 lysine 4 (H3K4M3) localization.
- Active and repressive histone modifications coexist in the Hoxa9 regulatory region.
- Cdx4 and menin bind to the same Hoxa9 regulatory region and co-activate transcription.
- Menin ablation prevents Cdx4 chromatin access and reduces histone modifications at the Hoxa9 locus.
Conclusions:
- A functional link exists between Cdx4, menin, and histone modifications in regulating Hoxa9.
- This interplay is critical for Hoxa9 regulation in hematopoietic cells.
- Findings provide mechanistic insights into Hoxa9 gene control during hematopoiesis.
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